Temporal imprecision of phase coherence in schizophrenia and psychosis-dynamic mechanisms and diagnostic marker.

Schizophrenia (SCZ) is a complex disorder in which various pathophysiological models have been postulated. Brain imaging studies using EEG/MEG and fMRI show altered amplitude and, more recently, decrease in phase coherence in response to external stimuli. What are the dynamic mechanisms of such phase incoherence, and can it serve as a differential-diagnostic marker? Addressing this gap in our knowledge, we uniquely combine a review of previous findings, novel empirical data, and computational-dynamic simulation. The main findings are: (i) the review shows decreased phase coherence in SCZ across a variety of different tasks and frequencies, e.g., task- and frequency-unspecific, which is further supported by our own novel data; (ii) our own data demonstrate diagnostic specificity of decreased phase coherence for SCZ as distinguished from major depressive disorder; (iii) simulation data exhibit increased phase offset in SCZ leading to a precision index, in the millisecond range, of the phase coherence relative to the timing of the external stimulus. Together, we demonstrate the key role of temporal imprecision in phase coherence of SCZ, including its mechanisms (phase offsets, precision index) on the basis of which we propose a phase-based temporal imprecision model of psychosis (PTP). The PTP targets a deeper dynamic layer of a basic disturbance. This converges well with other models of psychosis like the basic self-disturbance and time-space experience changes, as discussed in phenomenological and spatiotemporal psychopathology, as well as with the models of aberrant predictive coding and disconnection as in computational psychiatry. Finally, our results show that temporal imprecision as manifest in decreased phase coherence is a promising candidate biomarker for clinical differential diagnosis of SCZ, and more broadly, psychosis.

The nested hierarchical model of self and its non-relational vs relational posttraumatic manifestation: an fMRI meta-analysis of emotional processing.

Different kinds of traumatic experiences like natural catastrophes vs. relational traumatic experiences (e.g., sex/physical abuse, interpersonal partner violence) are involved in the development of the self and PTSD psychopathological manifestations. Looking at a neuroscience approach, it has been proposed a nested hierarchical model of self, which identifies three neural-mental networks: (i) interoceptive; (ii) exteroceptive; (iii) mental. However, it is still unclear how the self and its related brain networks might be affected by non-relational vs relational traumatic experiences. Departing from this background, the current study aims at conducting a meta-analytic review of task-dependent fMRI studies (i.e., emotional processing task) among patients with PTSD due to non-relational (PTSD-NR) and relational (PTSD-R) traumatic experiences using two approaches: (i) a Bayesian network meta-analysis for a region-of-interest-based approach; (ii) a coordinated-based meta-analysis. Our findings suggested that the PTSD-NR mainly recruited areas ascribed to the mental self to process emotional stimuli. Whereas, the PTSD-R mainly activated regions associated with the intero-exteroceptive self. Accordingly, the PTSD-R compared to the PTSD-NR might not reach a higher symbolic capacity to process stimuli with an emotional valence. These results are also clinically relevant in support of the development of differential treatment approaches for non-relational vs. relational PTSD.

Intrinsic neural timescales relate to the dynamics of infraslow neural waves.

The human brain is a highly dynamic organ that operates across a variety of timescales, the intrinsic neural timescales (INT). In addition to the INT, the neural waves featured by its phase-related processes including their cycles with peak/trough and rise/fall play a key role in shaping the brain's neural activity. However, the relationship between the brain's ongoing wave dynamics and INT remains yet unclear. In this study, we utilized functional magnetic resonance imaging (fMRI) rest and task data from the Human Connectome Project (HCP) to investigate the relationship of infraslow wave dynamics [as measured in terms of speed by changes in its peak frequency (PF)] with INT. Our findings reveal that: (i) the speed of phase dynamics (PF) is associated with distinct parts of the ongoing phase cycles, namely higher PF in peak/trough and lower PF in rise/fall; (ii) there exists a negative correlation between phase dynamics (PF) and INT such that slower PF relates to longer INT; (iii) exposure to a movie alters both PF and INT across the different phase cycles, yet their negative correlation remains intact. Collectively, our results demonstrate that INT relates to infraslow phase dynamics during both rest and task states.

Repertoire of timescales in uni - and transmodal regions mediate working memory capacity.

Working memory (WM) describes the dynamic process of maintenance and manipulation of information over a certain time delay. Neuronally, WM recruits a distributed network of cortical regions like the visual and dorsolateral prefrontal cortex as well as the subcortical hippocampus. How the input dynamics and subsequent neural dynamics impact WM remains unclear though. To answer this question, we combined the analysis of behavioral WM capacity with measuring neural dynamics through task-related power spectrum changes, e.g., median frequency (MF) in functional magnetic resonance imaging (fMRI). We show that the processing of the input dynamics, e.g., the task structure's specific timescale, leads to changes in the unimodal visual cortex's corresponding timescale which also relates to working memory capacity. While the more transmodal hippocampus relates to working memory capacity through its balance across multiple timescales or frequencies. In conclusion, we here show the relevance of both input dynamics and different neural timescales for WM capacity in uni - and transmodal regions like visual cortex and hippocampus for the subject's WM performance.

Overcoming the translational crisis of contemporary psychiatry - converging phenomenological and spatiotemporal psychopathology.

Despite all neurobiological/neurocomputational progress in psychiatric research, recent authors speak about a 'crisis of contemporary psychiatry'. Some argue that we do not yet know the computational mechanisms underlying the psychopathological symptoms ('crisis of mechanism') while others diagnose a neglect of subjectivity, namely first-person experience ('crisis of subjectivity'). In this perspective, we propose that Phenomenological Psychopathology, due to its focus on first-person experience of space and time, is in an ideal position to address the crisis of subjectivity and, if extended to the brain's spatiotemporal topographic-dynamic structure as key focus of Spatiotemporal Psychopathology, the crisis of mechanism. We demonstrate how the first-person experiences of space and time differ between schizophrenia, mood disorders and anxiety disorders allowing for their differential-diagnosis - this addresses the crisis of subjectivity. Presupposing space and time as shared features of brain, experience, and symptoms as their "common currency", the structure of abnormal space and time experience may also serve as template for the structure of the brain's spatiotemporal neuro-computational mechanisms - this may address the crisis of mechanism. Preliminary scientific evidence in our examples of schizophrenia, bipolar disorder, anxiety disorder, and depression support such clinically relevant spatiotemporal determination of both first-person experience (crisis of subjectivity) and the brain's neuro-computational structure (crisis of mechanism). In conclusion, converging Phenomenological Psychopathology with Spatiotemporal Psychopathology might help to overcome the translational crisis in psychiatry by delineating more fine-grained neuro computational and -phenomenal mechanisms; this offers novel candidate biomarkers for diagnosis and therapy including both pharmacological and non-pharmacological treatment.

Brain-wide changes in excitation-inhibition balance of major depressive disorder: a systematic review of topographic patterns of GABA- and glutamatergic alterations.

The excitation-inhibition (E/I) imbalance is an important molecular pathological feature of major depressive disorder (MDD) as altered GABA and glutamate levels have been found in multiple brain regions in patients. Healthy subjects show topographic organization of the E/I balance (EIB) across various brain regions. We here raise the question of whether such EIB topography is altered in MDD. Therefore, we systematically review the gene and protein expressions of inhibitory GABAergic and excitatory glutamatergic signaling-related molecules in postmortem MDD brain studies as proxies for EIB topography. Searches were conducted through PubMed and 45 research articles were finally included. We found: i) brain-wide GABA- and glutamatergic alterations; ii) attenuated GABAergic with enhanced glutamatergic signaling in the cortical-subcortical limbic system; iii) that GABAergic signaling is decreased in regions comprising the default mode network (DMN) while it is increased in lateral prefrontal cortex (LPFC). These together demonstrate abnormal GABA- and glutamatergic signaling-based EIB topographies in MDD. This enhances our pathophysiological understanding of MDD and carries important therapeutic implications for stimulation treatment.

Deciphering the interplay between psychopathological symptoms, sensorimotor, cognitive and global functioning: a transdiagnostic network analysis.

BACKGROUND: Understanding the relationship between psychopathology and major domains of human neurobehavioral functioning may identify new transdiagnostic treatment targets. However, studies examining the interrelationship between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample are lacking. We hypothesized a close relationship between sensorimotor and cognitive functioning in a transdiagnostic patient sample. METHODS: We applied network analysis and community detection methods to examine the interplay and centrality [expected influence (EI) and strength] between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample consisting of 174 schizophrenia spectrum (SSD) and 38 mood disorder (MOD) patients. All patients (n = 212) were examined with the Positive and Negative Syndrome Scale (PANSS), the Heidelberg Neurological Soft Signs Scale (NSS), the Global Assessment of Functioning (GAF), and the Brief Cognitive Assessment Tool for Schizophrenia consisted of trail making test B (TMT-B), category fluency (CF) and digit symbol substitution test (DSST). RESULTS: NSS showed closer connections with TMT-B, CF, and DSST than with GAF and PANSS. DSST, PANSS general, and NSS motor coordination scores showed the highest EI. Sensory integration, DSST, and CF showed the highest strength. CONCLUSIONS: The close connection between sensorimotor and cognitive impairment as well as the high centrality of sensorimotor symptoms suggests that both domains share aspects of SSD and MOD pathophysiology. But, because the majority of the study population was diagnosed with SSD, the question as to whether sensorimotor symptoms are really a transdiagnostic therapeutic target needs to be examined in future studies including more balanced diagnostic groups.

Increased noise relates to abnormal excitation-inhibition balance in schizophrenia: a combined empirical and computational study.

Electroencephalography studies link sensory processing issues in schizophrenia to increased noise level-noise here is background spontaneous activity-as measured by the signal-to-noise ratio. The mechanism, however, of such increased noise is unknown. We investigate if this relates to changes in cortical excitation-inhibition balance, which has been observed to be atypical in schizophrenia, by combining electroencephalography and computational modeling. Our electroencephalography task results, for which the local field potentials can be used as a proxy, show lower signal-to-noise ratio due to higher noise in schizophrenia. Both electroencephalography rest and task states exhibit higher levels of excitation in the functional excitation-inhibition (as a proxy of excitation-inhibition balance). This suggests a relationship between increased noise and atypical excitation in schizophrenia, which was addressed by using computational modeling. A Leaky Integrate-and-Fire model was used to simulate the effects of varying degrees of noise on excitation-inhibition balance, local field potential, NMDA current, and . Results show a noise-related increase in the local field potential, excitation in excitation-inhibition balance, pyramidal NMDA current, and spike rate. Mutual information and mediation analysis were used to explore a cross-level relationship, showing that the cortical local field potential plays a key role in transferring the effect of noise to the cellular population level of NMDA.

[German version of the Northoff scale for subjective experience in catatonia (NSSC-dv) : A validated instrument for examination of the subjective experience in catatonia]. / Deutsche Version der Northoff Skala für subjektives Erleben bei Katatonie (NSSC-dv) : Ein validiertes Messinstrument zur Erfassung des subjektiven Erlebens bei Katatonie.

Patients with catatonia often show serious motor, affective and behavioral symptoms, behind which the subjective experience often remains hidden. Therefore, this study disseminates our own systematic empirical investigation of the subjective experience of catatonia patients to a German-speaking audience of clinicians and researchers. Based on current evidence and the clinical experience of the authors, the self-report questionnaire Northoff Scale for Subjective Experience in Catatonia (NSSC) was modified, extended and validated and now consists of 26 items capturing the subjective experience of catatonia in its clinical diversity. A total of 46 patients with catatonia according to the International Classification of Diseases (11th revision, ICD-11) were asked about their subjective experience during the acute phase of the disease using the NSSC. The NSSC showed high internal consistency (Cronbach's alpha = 0.91). The NSSC total score was significantly associated with the Northoff Catatonia Rating Scale (NCRS; r = 0.46; p < 0.05), the total score of the Positive and Negative Syndrome Scale (PANSS; r = 0.30; p < 0.05), the Brief Psychiatric Rating Scale (BPRS; r = 0.33; p < 0.05), and Trait Anxiety (STAI; r = 0.64; p < 0.01), supporting its validity. Preliminary validation of the NSSC revealed good psychometric properties. The NSSC is a useful instrument for routine clinical use to assess the subjective experience of patients with catatonia in order to provide tailored psychotherapeutic interventions.

Intrinsic neural timescales mediate the cognitive bias of self - temporal integration as key mechanism.

Our perceptions and decisions are not always objectively correct as they are featured by a bias related to our self. What are the behavioral, neural, and computational mechanisms of such cognitive bias? Addressing this yet unresolved question, we here investigate whether the cognitive bias is related to temporal integration and segregation as mediated by the brain's Intrinsic neural timescales (INT). Using Signal Detection Theory (SDT), we operationalize the cognitive bias by the Criterion C as distinguished from the sensitivity index d'. This was probed in a self-task based on morphed self- and other faces. Behavioral data demonstrate clear cognitive bias, i.e., Criterion C. That was related to the EEG-based INT as measured by the autocorrelation window (ACW) in especially the transmodal regions dorsolateral prefrontal cortex (dlPFC) and default-mode network (DMN) as distinct from unimodal visual cortex. Finally, simulation of the same paradigm in a large-scale network model shows high degrees of temporal integration of temporally distinct inputs in CMS/DMN and dlPFC while temporal segregation predominates in visual cortex. Together, we demonstrate a key role of INT-based temporal integration in CMS/DMN and dlPFC including its relation to the brain's uni-transmodal topographical organization in mediating the cognitive bias of our self.

Disrupted relationship between intrinsic neural timescales and alpha peak frequency during unconscious states - A high-density EEG study.

Our brain processes the different timescales of our environment's temporal input stochastics. Is such a temporal input processing mechanism key for consciousness? To address this research question, we calculated measures of input processing on shorter (alpha peak frequency, APF) and longer (autocorrelation window, ACW) timescales on resting-state high-density EEG (256 channels) recordings and compared them across different consciousness levels (awake/conscious, ketamine and sevoflurane anaesthesia, unresponsive wakefulness, minimally conscious state). We replicate and extend previous findings of: (i) significantly longer ACW values, consistently over all states of unconsciousness, as measured with ACW-0 (an unprecedented longer version of the well-know ACW-50); (ii) significantly slower APF values, as measured with frequency sliding, in all four unconscious states. Most importantly, we report a highly significant correlation of ACW-0 and APF in the conscious state, while their relationship is disrupted in the unconscious states. In sum, we demonstrate the relevance of the brain's capacity for input processing on shorter (APF) and longer (ACW) timescales - including their relationship - for consciousness. Albeit indirectly, e.g., through the analysis of electrophysiological activity at rest, this supports the mechanism of temporo-spatial alignment to the environment's temporal input stochastics, through relating different neural timescales, as one key predisposing factor of consciousness.

Scale-free dynamics of core-periphery topography.

The human brain's cerebral cortex exhibits a topographic division into higher-order transmodal core and lower-order unimodal periphery regions. While timescales between the core and periphery region diverge, features of their power spectra, especially scale-free dynamics during resting-state and their mdulation in task states, remain unclear. To answer this question, we investigated the ~1/f-like pink noise manifestation of scale-free dynamics in the core-periphery topography during rest and task states applying infra-slow inter-trial intervals up to 1 min falling inside the BOLD's infra-slow frequency band. The results demonstrate (1) higher resting-state power-law exponent (PLE) in the core compared to the periphery region; (2) significant PLE increases in task across the core and periphery regions; and (3) task-related PLE increases likely followed the task's atypically low event rates, namely the task's periodicity (inter-trial interval = 52-60 s; 0.016-0.019 Hz). A computational model and a replication dataset that used similar infra-slow inter-trial intervals provide further support for our main findings. Altogether, the results show that scale-free dynamics differentiate core and periphery regions in the resting-state and mediate task-related effects.

Spatiotemporal dedifferentiation of the global brain signal topography along the adult lifespan.

Age-related variations in many regions and/or networks of the human brain have been uncovered using resting-state functional magnetic resonance imaging. However, these findings did not account for the dynamical effect the brain's global activity (global signal [GS]) causes on local characteristics, which is measured by GS topography. To address this gap, we tested GS topography including its correlation with age using a large-scale cross-sectional adult lifespan dataset (n = 492). Both GS topography and its variation with age showed frequency-specific patterns, reflecting the spatiotemporal characteristics of the dynamic change of GS topography with age. A general trend toward dedifferentiation of GS topography with age was observed in both spatial (i.e., less differences of GS between different regions) and temporal (i.e., less differences of GS between different frequencies) dimensions. Further, methodological control analyses suggested that although most age-related dedifferentiation effects remained across different preprocessing strategies, some were triggered by neuro-vascular coupling and physiological noises. Together, these results provide the first evidence for age-related effects on global brain activity and its topographic-dynamic representation in terms of spatiotemporal dedifferentiation.

Rest-task modulation of fMRI-derived global signal topography is mediated by transient coactivation patterns.

Recent resting-state functional MRI (fMRI) studies have revealed that the global signal (GS) exhibits a nonuniform spatial distribution across the gray matter. Whether this topography is informative remains largely unknown. We therefore tested rest-task modulation of GS topography by analyzing static GS correlation and dynamic coactivation patterns in a large sample of an fMRI dataset (n = 837) from the Human Connectome Project. The GS topography in the resting state and in seven different tasks was first measured by correlating the GS with the local time series (GSCORR). In the resting state, high GSCORR was observed mainly in the primary sensory and motor regions, whereas low GSCORR was seen in the association brain areas. This pattern changed during the seven tasks, with mainly decreased GSCORR in sensorimotor cortex. Importantly, this rest-task modulation of GSCORR could be traced to transient coactivation patterns at the peak period of GS (GS-peak). By comparing the topography of GSCORR and respiration effects, we observed that the topography of respiration mimicked the topography of GS in the resting state, whereas both differed during the task states; because of such partial dissociation, we assume that GSCORR could not be equated with a respiration effect. Finally, rest-task modulation of GS topography could not be exclusively explained by other sources of physiological noise. Together, we here demonstrate the informative nature of GS topography by showing its rest-task modulation, the underlying dynamic coactivation patterns, and its partial dissociation from respiration effects during task states.

Intrinsic dynamics and topography of sensory input systems.

The brain is continuously bombarded by external stimuli, which are processed in different input systems. The intrinsic features of these sensory input systems remain yet unclear. Investigating topography and dynamics of input systems is the goal of our study in order to better understand the intrinsic features that shape their neural processing. Using a functional magnetic resonance imaging dataset, we measured neural topography and dynamics of the input systems during rest and task states. Neural dynamics were probed by scale-free activity, measured with the power-law exponent (PLE), as well as by order/disorder as measured with sample entropy (SampEn). Our main findings during both rest and task states are: 1) differences in neural dynamics (PLE, SampEn) between regions within each of the three sensory input systems 2) differences in topography and dynamics among the three input systems; 3) PLE and SampEn correlate and, as demonstrated in simulation, show non-linear relationship in the critical range of PLE; 4) scale-free activity during rest mediates the transition of SampEn from rest to task as probed in a mediation model. We conclude that the sensory input systems are characterized by their intrinsic topographic and dynamic organization which, through scale-free activity, modulates their input processing.

It's in the Timing: Reduced Temporal Precision in Neural Activity of Schizophrenia.

Studies of perception and cognition in schizophrenia (SCZ) show neuronal background noise (ongoing activity) to intermittently overwhelm the processing of external stimuli. This increased noise, relative to the activity evoked by the stimulus, results in temporal imprecision and higher variability of behavioral responses. What, however, are the neural correlates of temporal imprecision in SCZ behavior? We first report a decrease in electroencephalography signal-to-noise ratio (SNR) in two SCZ datasets and tasks in the broadband (1-80 Hz), theta (4-8 Hz), and alpha (8-13 Hz) bands. SCZ participants also show lower inter-trial phase coherence (ITPC)-consistency over trials in the phase of the signal-in theta. From these ITPC results, we varied phase offsets in a computational simulation, which illustrated phase-based temporal desynchronization. This modeling also provided a necessary link to our results and showed decreased neural synchrony in SCZ in both datasets and tasks when compared with healthy controls. Finally, we showed that reduced SNR and ITPC are related and showed a relationship to temporal precision on the behavioral level, namely reaction times. In conclusion, we demonstrate how temporal imprecision in SCZ neural activity-reduced relative signal strength and phase coherence-mediates temporal imprecision on the behavioral level.

From temporal to spatial topography: hierarchy of neural dynamics in higher- and lower-order networks shapes their complexity.

The brain shows a topographical hierarchy along the lines of lower- and higher-order networks. The exact temporal dynamics characterization of this lower-higher-order topography at rest and its impact on task states remains unclear, though. Using 2 functional magnetic resonance imaging data sets, we investigate lower- and higher-order networks in terms of the signal compressibility, operationalized by Lempel-Ziv complexity (LZC). As we assume that this degree of complexity is related to the slow-fast frequency balance, we also compute the median frequency (MF), an estimation of frequency distribution. We demonstrate (i) topographical differences at rest between higher- and lower-order networks, showing lower LZC and MF in the former; (ii) task-related and task-specific changes in LZC and MF in both lower- and higher-order networks; (iii) hierarchical relationship between LZC and MF, as MF at rest correlates with LZC rest-task change along the lines of lower- and higher-order networks; and (iv) causal and nonlinear relation between LZC at rest and LZC during task, with MF at rest acting as mediator. Together, results show that the topographical hierarchy of lower- and higher-order networks converges with their temporal hierarchy, with these neural dynamics at rest shaping their range of complexity during task states in a nonlinear way.

From Molecular to Behavior: Higher Order Occipital Cortex in Major Depressive Disorder.

Medial prefrontal cortex (MPFC) and other regions like the occipital cortex (OC) exhibit abnormal neural activity in major depressive disorder (MDD). Their relationship to specific biochemical, psychophysical, and psychopathological changes remains unclear, though. For that purpose, we focus on a particular subregion in OC, namely middle temporal (MT) visual area that is known to mediate the perception of visual motion. Using high-field 7 T magnetic resonance imaging (MRI), including resting state functional MRI and proton magnetic resonance spectroscopy, the amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent signal in MT, MT-seeded functional connectivity (FC), and gamma-aminobutyric acid (GABA) in MT were investigated. Applying the vision motion psychophysical task, the motion suppression index of subjects was also examined. We demonstrate significantly elevated neural variability (as measured by ALFF) in MT together with decreases in both MT GABA and motion suppression in our MDD sample. Unlike in healthy subjects, MT neural variability no longer modulates the relationship of MT GABA and motion suppression in MDD. MT also exhibits reduction in global inter-regional FC to MPFC in MDD. Finally, elevated MT ALFF relates to specifically retardation in behavior as measured by the Hamilton subscore. Together, MT provides a strong candidate for biomarker in MDD.

The self and our perception of its synchrony - Beyond internal and external cognition.

The self is the core of our mental life which connects one's inner mental life with the external perception. Since synchrony is a key feature of the biological world and its various species, what role does it play for humans? We conducted a large-scale psychological study (n = 1072) combining newly developed visual analogue scales (VAS) for the perception of synchrony and internal and external cognition complemented by several psychological questionnaires. Overall, our findings showed close connection of the perception of synchrony of the self with both internal (i.e., body and cognition) and external (i.e., others, environment/nature) synchrony being associated positively with adaptive and negatively with maladaptive traits of self. Moreover, we have demonstrated how external (i.e., life events like the COVID-19 pandemic) variables modulate the perception of the self's internal-external synchrony. These findings suggest how synchrony with self plays a central role during times of uncertainty.

Neural responses to emotional stimuli across the dissociative spectrum: Common and specific mechanisms.

AIM: Departing from existing neurobiological models of dissociation, the current study aims at conducting a quantitative meta-analytic review of neural responses to emotional stimuli among individuals ascribed to the dissociative spectrum (DS). Accordingly, the study explored common and specific brain mechanisms across borderline personality disorder, conversion/somatoform disorders, posttraumatic stress disorder, posttraumatic stress disorder related to repeated interpersonal traumatic experiences, and dissociative disorders. METHODS: The meta-analysis included studies that administered emotional stimuli during functional magnetic resonance imaging acquisition among individuals included in the DS. There were two conducted meta-analytic procedures: (i) a Bayesian network meta-analysis for a region-of-interest-based approach; and (ii) robust voxel-based approach. RESULTS: Forty-four independent studies were included for a total of 1384 individuals (DS = 741 patients). The network meta-analysis showed specific patterns of neural activity considering an extended brain network involved in emotion regulation for each condition ascribed to the DS. The voxel-based meta-analysis highlighted an increased activity of dorsal anterior cingulate cortex as a common neurological signature of the DS. CONCLUSION: The common neural feature of the DS captures an implicit appraisal of emotion-eliciting stimuli as threatening and/or noxious for mental and physical integrity of the individual together with painful subjective experiences associated with physiological emotional reactions. Specific brain responses across the DS suggested the engagement in different mechanisms to address emotional stimuli, including implicit avoidance reactions and attempts to overcontrol of affective states together with a disruption of integrative processes of emotional mind-body features.